Our preliminary results indicate small red blood cell membrane fragments are found in the circulation of patients with sickle cell anemia and that monocyte bactericidal capacity may be defective in these same patients. This suggests a generalized reticuloendothelial defect most prominently involving the spleen of patients with sickle cell anemia that leaves them vulnerable to overwhelming pneumococcal infection. If we confirm our preliminary findings, we will attempt to replicate this defect in vitro by incubating heat-generated red blood cell fragments and fragments isolated by gradient centrifugation from patients with sickle cell anemia with normal monocytes. Conversely, we will attempt restoration of normal bactericidal capacity by incubation of monocytes isolated from the peripheral blood of patients with sickle cell anemia in normal serum. Red blood cell fragments from patients with sickle cell anemia will be further characterized with respect to morphology, size, presence of characteristic membrane antigens and mechanism of uptake by the monocyte. Monocyte bactericidal capacity will be correlated with the "pocked erythrocyte count" which has recently been suggested as an index of reticuloendothelial dysfunction. Kinetic analysis of the initial rates of ingestion of labeled bacteria and fragments in the presence and absence of varying concentrations of fragments will determine the role of competitive inhibition in depression of monocyte bactericidal capacity. These studies represent an unexplored approach to the major clinical hazard of children with sickle cell anemia - namely, overwhelming septicemia.